Note: Descriptions are shown in the official language in which they were submitted.
2130609
I
ST~ 7Fn P~OXIDI~ CnNr~9/Nl~G
F~l/n~2E
~ACI~ OUNO OF 7~1~1NV~l~Q~Jf
The h~vanllon r~l~tes to dental products for proi-.uli.-~ health In the oral cavlty.
10 Orsl com~slllons contalnln~ both a p~fO. Id~ and wdlum blca.l~r~l~ have
boen acclalmod by th~ d~ntal pro~a~slon, e 5peci~11y throu~h the work of Keyes.
See Ke~e~ et al. ~rlcdoi)lk~ and Oral Hyghne~, .lanuary 1~78, p~ 51-56.
Formubtlons b~bod on the Keyes ~acl.riDlD~y, especlally the peroxlde
cG~,~pono.n~arepartlcul~tlypronotodoco~pos;lio.-. Thellteratureh ,pG.t~,d
15 conslder~ble research dlrectQd at the stability problem. For instance, see U.S.
Patent 3,577,~21 ~;ch~"Er), U.S. Pat~nt 4,837,008 ~Rudy et al), U.S. Patant
4,130,501 (L~), U.S. 4,89S,721 (~ruckerl ar~d U.5. Pstsnt 4,343,785
(Schmollca). A qulte sucGe s~ful approach to the pr~bl~ has Il~vol~Gd pi~sical
so~reçi~tlon of tne peroxld~ into a c~--,p~ t ~eparate from c~rea~ivo
~0 In~redlen~. U.S. Patcnt 4,849,213, U.S. Patent4,687,663 uld U.S. Pat~nt
4,528,180, all to Scl,aerfer, d~sclose a packa~e with a dual-con~a.l"h,.,t
re~pectlvel~/ storln~ a p~ xlde ~el and a blcal l,Gnate pa~te.
n~ J l~hnclu a~ Is Jesc.Il,ed In U.S. Patent4,487,757 ~Kio~r~cp'~u) whlch
25 ~1~ S ~ eb a toothpaste In a dlspenserthat physically sepuates sodium bic~rl.~
ate from acldic ;..~redlenls, e.~. citrlc or ascorbic~cids, to prevent contact
r~l~e~ prlor to us~e.
.,
2 2130609
In U.S. Patent 4,788.052. U.S. Patent 4,839,156 end U.S. P~tent 4,839,157
~all to N~ et ~I) are d~bc ,bed equeous hydro~en peroxide ~el ~ ~tir~lceo that
c~n be sbblllzed bV use of a combination of l~drophilllc and hydrophoblc furned
811ice. Aqueous moull)rinses have been described in U.S. P~tent 5,104,~44
5 ~Dou~b~ that contaln hydro~en per ~ dH. Al~o present ot relatlvely low
co,.~e.lt,~lh,..s ore such additives as zinc el,':riJe, s-J-r..~ rit, sodium cltrate
and cltrlc acld. It ~hould be noted that nelther the N~ et al nor Dou~las pd~
Include fluorlde anlons wlthln the su~ested c-l.nl ~,v;li-"-s.
10 From the af~.~..,eruicnGd att. it bece.ll~ 3ppa,ent that h~d-~a~n peroxlde
co..~>odlllol1~ should be formulated as simply as posslble ~o mlnlmlze polonll
Inte~lons between the pt;ru)~ e end the rem~lnlng In~sd's.-~s.
Fiuorldo anion 18 known by those skilled in the art as a de3l~b,111~1n~ faGtor in
15 porGI d~ ~els. The deslrablllty of acl.~ ntlcub4 proucllGn for oral
products h~ ro,..,~tl,d formul~ors to ~eek a s8tl5~ac~0ry means to ~llow
fluorlde Incorpo~llon. In U.S. Patent 5,037.633 and U.S. Patent 5,037,634
to Wllllams ot al. and Zlemklewlcz et al., resp~cli-/el~v, the problem was solved
by h~cofpor~tlno todlum fl~oride into a b'~.bon~le paste l~lt~,.,ded to be
20 co~xtruded ~rlth a pcroxlde ~el. each from a separate ~,n~ ,nl of a
dual~omp~rtment contalner. S~e also U.S. Patent 5,0~9,417 (Willl~ms et al.
dotallln~ the peroxlde l~chnn~y.
Whlls r~le~stln~ fluoride to the blcarbonate con~pone. ~I may solve the an-lco,ri~s
25 ,~.et'e..., there stlll remalns the problem of dlsp~nsin~ a co,-st~nt volum~ of
both pcr~ el end blcarbonate paste; accurate dosa~e of fluoride bas~d on
~otel ~nllrrloe volurne Is thereby ensured. Only wltl a speclal, costly pump 18
such pr~c:~e d~llver-,r ~chlevable.
J ~ 'Vl
Con~qu~ntly, ~ t~ ha~ been sou~ht whlch p~n~ both the blcarbonate
and the p6.0xlde co...pononts to each I~CGI~O~Ia sn id~rltlcal fluorld~
~.~tlCCrl6~ o~ent lhereb~ ellmlnatln~ need for a costl~ pump.
5 iBey~nd ~blll~tlon, any new anlicadas ~y~tem mu~ havs consumer
s~ti~l,ctory ta~e ~nd hsve no disruptive influcnce upon rl,~o!ooy, prociuctcoloror other physlc~ 1 PalLn~ al~-
n~c~nlly it has been rapo. laJ In U.S. Patent 5,217,710 ~Willi~ t ~1) th~t tin10 co.--~)ound~, e~p~ tanno.ls ion, may stabilke hydro~en p~roxlde In the
pt~s~nc~ of a f~uorlde compounci. Unfortunately, ther~ nre n~o problems wl~h
thk ~II~ID~. The first is thst stannous lons l~ rt sn un~atisfwtor~
m~alllc teste to the othe. lJJI~ fine or~anoleptic prope. L~s of the dont~l compo-
sltlon~. 5acon.1~r, the tln compound~ h~ve c~u~d sevcrc corroslve plttln~ of
1~ stainless ~toel ~~e~,t~r~ In which the dental pr~dw~ w~ m~nuf~ctured.
Accordingly, it is an object of the present invention to provide a peroxide-
containing composition capable of use with a bicarbonate composition
20 wherein both compositions contain a fluoride anticaries agent and there is
no adverse effect upon product stability. The peroxide composition and the
bicarbonate composition may be held in separate compartments of a dual-
compartment delivery system and each of the compositions may contain an
25identical fluoride anticaries agent.
4 ~ fi f~
The composition should have consumer-acceptable taste and maintain
color, e.g. blue.
Peroxide decomposition should be inhibited while still maintaining a clear
gel and the fluoride anticaries agent and stabilizing system should have no
adverse corrosive effect upon stainless steel manufacturing vessels.
SUMMARY OF THE INVENTION
An oral dental product comprising:
a first composition comprising:
(i) from 0.1 to 10% by weight of a peroxygen compound;
(ii) a physiologically-acceptable fluoride-containing compound
present in an effective amount to inhibit formation of caries
on teeth; and
(iii) a zinc compound present in an effective amount to stabilize
the peroxygen compound against decomposition by the
fluoride-containing compound,
and a second composition comprising from 0.5 to 80% by weight of an
alkalimetal bicarbonate and a physiologically~acceptable fluoride-
containing compound present in an effective amount to inhibit
formation of caries on teeth, the first and the second composition
being held in a separate compartment of a dual-compartment
dlspenser.
~ . ,~ I
J 61~ (V)
a~TAlLE~ /~SC~P7~nN
Now It ha~ been J~ red that zinc compounds hav~ the ~ AI e~t~d ablllt~
to Jtsblltze hl~d~ca~n peroxlde In tho pre~ence of a flwrldc co~pounq such
~odlum fluor~de.
Thw, as ~ first cssen~ wi"ponenl there is r~quired a cG,--pound, esi~ec~
~ salt, dellvo.l~.~ zlnc ions. B~ thc t~rm ~zinc lon" i8 meant that tbe zlnc-atom
portion of a ,n~le CLle of the zlnc compound in the solid or undisbcci~ted stato,
i5 cspnbb of bein~ dlssocl3ted into simple or complex zinc lons, especbll~
when . p~r~ed In an aqueous medium. Examples of the cG-,lpound~ th~t may
e~l ~n 71rc ~
/
~ u~u~ ~v~
213~9
c~. bo.)~t~, hexofruoroslllcate, ~,~.up~,o 6[1~1~tO, slllo~to, sulphate and tltlna~.
Or~nic anlons are thos~ havin~ from 2 to 22 carbon atoms wlth a cl~r~vJ
~roup selected from CL. l,o~-yl~t~, ~ulp~.v, l~t-" sulphate ar~ phospnate~ Specific
oxample~ Include, but ~re not llmited to, ac~lale, I,~n.c~al.J, citrste"Jly~ e,
5 lactate, pl ,~ Iphonate, salicylatc, tsrtrate, acetyld~"onat~., maleate,
succlnflt~, as~rl~ate, and ~luconate. Most prererreci is zinc citrste.
The zlnc salts wlll ~en~t~lly be pfCSe~ in the dental co,.,po~l~ion~ of the
lGn in ~n amount from ebout 0.01 tO about 10%, pre~r~bly between
10 about 0.1 and 5%, optlmally bel~r~rvo,, about 0.2 and 196 by wei~ht. When it
is deslrod to have e clear (at le~st tr~nslucen~) ~el, th~ level of zinc salt shouki
ran~e ~rom about 0.1 to 0.5%.
Another Impor~nt co~..pon~nl of the oral col"p~s'tio,- i~ th~t of a fluorlde
15 ~ntlc~rles cv-,.pound. Illu~t~ oS Sluorld~ compourKis are sodlum fluoride,
Jum tluorlde, calclum fluorlde, ...a~nes'u-n fluoride, stsnnous Ruoride,
~a.~)ous r~fl~Jorophosphal~, sodlum mo.~vnuoruphos~Jl.ate and copper
fluorldo. Thes~ ~ources should release an~Jher~, from about 25 to 3500 ppm
of fl~lorlde lon. The ~n~led~ O ~ent wlll b~ pre~ent in an arno-lnt from about
20 0.01 to ~bout S%, pr~fl~rably from about 0.1 to ~bout ~.596, optimall~y b~tw~en
about 0.2 and about 1.5% by wei~ht of the p~roxide coi,.rosl(lon.
A varlety of peroxy~en c~,-,pollnds may be employed including urea l,Gr~"-We,
calclum p~rox'~, h~l.o~en peroxlde and the s~lts of perl,o.atn, per~ilicate,
25 perlJho~pl.~.te and percsrbonate. Th~ most sultable for this inventlon is hydro-
~en p~lde. ~he emount of the peroxy~en compound may ran~e from about
û. 1 to about 1 og6 by weight. In terms ot active w~i~ht hydro~en peroxide, the
amount wlll r~n~e from about 0.5 to about 5%, pr~ferably from about 0.8 to
~ v lv~ ~l
213Q609
ebout 496, optin~lly benNeen sbout 1 ~nd 3% by wel~ht.
Oral compo~ltlons of the pr~senl l~,~.,ntlon may be In the fofm of elther a
toothpa~te, ~ ~el, a tablet, a p. ~:d~. or ~ mouthwash.
Water may b~ pre3em In the C0--1pGS;liOnS In amounts ran~in~ fronl about 20
to ebout 9596 by wei~ht, When the peroxide composition Is 8 ~el, the amount
of w~ter rn~y rsn~e from about 30 to about 55%, optlmally b~t~een about 35
and ~% by w~l~ht.
Structu~ants are ne&_ss~ where the peroxide C0-1-pQ~ Gn 1~; in the form of a
~1. Most sul~ble ~s the s~uctur~nt ~re the polyoxyethylene-polyoxypropylene
copoly.net~ whero the hydn,phe~l~ portlon, repr~sented by ~C~HoO), hs8 a
mobcubr wel~ht ren~ln~ from about 2,750 to 4,000 an~the hydrophllic
15 portlon, repre~emed by ~C211,0), c.u~lile~cs ~bout 70 to.~O% of the wol~ht of th~ CO~ y.l.3r. Commerclally the copoly"~ra are avallable from the BASF
Co~poratlon ~nderthe trad~ , Pluronlc F88, F99, F108 and ~127, Most
prato~l.,d l~ Pluronic F127 lI,~.eb,srt~r ,~r~.r~d to by Its CTF~ n~
Poloxomor 407~ whlch has a mslecu~r wel~ht ran~in~ from about 10,000 to
20 15,000, ~nd c~n~inln~ about 709~ of me hydrophillc polyoxyethylene mol~ty.
Amount8 oif the copoly."er can ran~e anywhere from 18 to 259~ by ~l~ht,
pref~r~bty b~_en 19 snd 24~6. Poloxamers are particularly sultable for this
l..~ron~lon LYce~Ee of th~ir wlde pH t ~ nc~, ~ood cGm~ ib;l;t~ with hydro~sn
pw~ ld~ end unlque ~el prop~ s.
Glyc~rol i8 cnother pr~ferred in~redient of the p~roxide composltion ~Ivhen in ~el
or rlnse form. Amounts of ~Iyoerol may ran~ from about 5 to about 60%,
pref~r~ly from sbout 5 tO 20% by wel~ht for t~ rinse snd from about 35 to
J 61 6~
8 ~ ~ 3 ~
45% by wel~ht for tho ~el.
Adlunct mlnor Ir,~,~dlonts msy elso be prc e.,l in the con~.p~sltlons of this
Ir.v~mlon. Included may be small amounts of colorant fbvor and z.~tloxldant.
Oral compositions of the present invention include besi~es a peroxide
co-nr ~lllv ~ on ~ddlllo-,al sepsrste bica~bon~ co,-l~ini--u com~oslllol~ each
held wlthln a ~ep~r~te container ~ tle for simultaneous d~ In
10 subs~ntlE~lly equal volumes for use In the mouth.
Th~ bicarbonate cG..,posillon wlll also contain a fluoride anticarles c~rs.pound~61e ~ed from the ~me fluorlde compounds in e~sentlally Identlc~l amounts to
those descrlbed h~r~. n~bove with respoct to the pe.uxtde cOI~ po~tlon.
15 E8peclally pr~r_r-~d iS sodium fluorid~. Bicalt~r~dt~. sa~ts will be pra~ent In
llmetal form ~xamplesof which are 80dlUlrl snd pot Yi Jm. Typlc~lly the
ConConlf~tlor, of blcsll,onet~ salt wlll ran~e from about 0.5 to about 8096,
preferably from ~bout 5 to about S096 optimally ba(~ n about 8 and ~bout
2096 by wel~lht of th~ total oombined dental product. The pH of the blcarbon-
20 ~te c~- Ir O ~liKion m~y r~n~e frorn about 7.0 to abo~n 9.5, most prefersoly about
8.0 to 9Ø When the blc~-~,onal~ col-,positlon 15 In tu~l,p~s~ or ~el ~orrn,
there wlll typlc~lly be includsd ~ n~tur~l or ;,~ tlc ll,lckel~ln~ a~ent In an
amount ~om about 0.1 to 10%, p-~f~ bly about 0.5 to 5~6 by wel~ht.
Thlcl~eners may include hydroxypropyl meth~l cellulose, hyd~oxyethyl cellulose,
25 sodlum c&.i-,,o~m~tl,~l cl~llulose, xanthan gum, ~ra~acanlh gum, karaya ~um,
~r~b~ ~um, Irlsh moss, st~rch, al~lna~es and car~a~eenans.
Su. 1~ 'C:tL. .ts tlre normally also included in Ihe bicarbon~te compositions. These
~.i, ,.. , . ~,~
J 6162 ~V)
2I3~6~3
surfactams may be of the anicnlc, nonionic, callon'C or ~,-,phot ic type. Most
preterred ere sodlum l~uryl sulfate, codium dode~ nLel~a SUIlOndl~ and
sodlum laurylsârcush~al~. Sulf~ d-lls are usually pr~e~l In an amount from
about 0.5 to nbout 5~6 by weight.
When In the form of a toothpaste or ~el, the bicarbonate co.r,p~sltions wlll
- norrn~lly Include an abraslve in a~d;t;on to the bica.t,on~le. Abraslves msy be
~ele t d ~rom water-lnsoluble alkall or ~Ik~llne earth me~l satt~ ot
met~pho~h~te nlVlP), c~lclum c~r~on~te, ~lumJn~te ~nd snlc~te. Especlsl~y
10 preferr~d ~re s~ dlce~cium phosph~tH ~nd calclum ce.bouet... Amounts of
the abraslve wlll range from about 5 to about 80% by wei~ht.
~rtsr control s~ents m~y be incorporated Into c~ Q6~0n~ of thl6 Ir-~ntlon.
Especlally effectlve wlll be ~ents contalnlng phosphorous. Inor~anlc
15 phosphorous t~rtar control s~ents may Include sodlllm trlpol~fphGs~hale ~r myof the wflter-soluble py.ophosphal~Osuch as disodium ~)~,u~Jl,o~phate, dlpot~s-
slum p~pl,a ;~h~te end mlxtures of these wlth telr~potanlllm
~,t..ph~sph~tos or tetra~odiurn p~.ophs sphat~s. Or~an-c phosphorous con~
pounds tinat may serve as tar~r control a~ents Include ~nly~h~sph~nat~s such
~0 ~s di~odlum ~lhan~ 1-hydroxy-1,1-diphosphonale (EHDP), ~n~ha,~Ji~ sphonk
acld, ~nd 2-phospt,o.~o~utane-1,2,~trica-boA~licacld.
Flavors are u8uelly pres e nt In both the p~roxido and, when sultable, blcal LonalG
c~n~po~l~lons These flavors rnay be based on olls of spearmlnt and
25 ptpper-,lint. ~x8r~plcs of ~ther flavorin~ ~na~ri~l~ include ~-,u,,ll-ol. clow,
wln~r~ .., eucalyptus and aniseed. Flavors may ran~e in conce"udliu.l from
about 0.1 to about 5% by wei~ht of the total composltlon.
J 6162 ~V~
,
2130609
.
.,v~ea~n' ~ n~ent~ such ~18 secchuin. sodlum ~ clo,-~le. aspe. l--...e, ~ucroso
and the llke may be includod at l~vels from about 0.1 to about 5% by wel~ht
of th~ tobl C~...,JO~I~IGI~.
5 Other oddltlves may also be IncG.,uGrOIed Into the or~l cG~IFQsltlons Includln~
~r.F~ tlves, 6111cones, other ~ ic or natural polymers such as G~ntrez
S-~7, and nntl~ln~lvltls actlves.
The ~ n:n~l ex~mples vvill more fully illustrate the embodlrnents of thls
10 Invenllon. All part~. percenla~es and proportions referred to hereln and In the
~ppended clalms a~e by wel~ht of the total ~o,n~,o~lliun unle~ v~ r-f~lse
~d.
E.~MPLE ~ ~
Typlcal of the pr~ent Invention i5 a peroxlde ~el w.,-p~sltlen whose
formulatlon k det8ihd under Table 1. 'rhe formulatlon of T~ble I may be Utlllz~dIn com,t l, .otlon wlm a blc~, bGnele co~npositiu" des~tled under Table IL each ot
20 tt-e c~n.~ ,n~ beln~ held in a ~epu~te CGIllp~ -,ent of a dual~"-~&. l--.ern
dl~penser.
~ .
J 61 62 (V~
,
11 21~6V9
...~ .
T~bk I
reroxlde Gel Con~. ~
1~4r. ~ P-r~l Wt.%
Pluron~c F127 20.000
8 ~'~yc~ 40,000
Hydl~Gr. Petoxide 13~% food ~rade) 4.285
Cltrlc Acld 0.~00
Sodlum Fluorlde 0.240
Zlnc Cltrate 0.200
FDJlC Blue 1 0.005
~ ~1 rh~rlc Acld ~85% w/w~ 0,150
D~lanl.~d water Babnce
Table n .
pic~r~o~Ate pACp Co-n~un~-lt
lr~ nt ~Wt.%
Polyol 11 (60r~JhGl and other su~srs) 48.710
Sylold ~3XX (~b~3~ . silica~ ~6.000
Sodlum E~lcL~ at~ 10.000
I'EG 32 (polyethylene ~lycol~ ~-000
Sylox 15x ~thlck~nln~ 8111ca) 4.600
Sodlum Lauryl Sulf~te 2.980
SD Alcohol 38B 2.850
Cellulo~e Gurn 0.800
M~ .tl.ol 0-500
Sodlum Sacch2rin 0.500
Sodium Fluorld~ 0.240
Tltanium Dloxlde ~' 0-300
D2'~ water Balance
J 6162 ~V~
12 2130
, _ ,
-
~AMae2
A ~erle~ of ~tablllty ax~,crlu.ents wer~ conducted to ov~luate the effect of ~Inc
citrate on s~bllizin~ a pe.oxTde ~el when fluorlde lon~ sre pr~se.-t in the
5 co...r ~filtion.
The test employed was the PeroAide Stablllty/Stress Test IPSST~ mple~
were ~ a~od to ~ccele.~led a~ln~ ~t a ~ -psr~ture ot 95-C over a ~hour
perlod. These a~in~ condlllGos were found to h~ve ~lood correl~ion ~th
10 3 o~cnt~ sto~e stablllty testin~ at 105~F. P~ra: 'da contont of the ~el w~
a~sayed by o-~hlkl~ ~sslum lodlde to lodlne snd tl~lslln,J wlth ~odlum
th'~sul~dl~ on ~n auto-titrator fltted Witll a redox ~l .,tl~de.
T~bb 11
1~ PSST Rewl~
Inl~bl % HZ02 After 6 llou~ ot 95~C
Recovery
NQ Fluorlde
1 Month at RT 1.48 1.36
91.88
1 Month ~t 105~F 1.47 1.34
91 .1 ~
F1uo~1de lO 74% t~) wlth Z~nc
251 Month ~t RT 1.46 1.46
1 00.00
Month at 106~F 1 .47 '1.43
.97
i
,
. . - - ,
J~1~2(V)
.
'~- 13 21~603
~orlde (0.~4% l~bFI Wl*lou~ Zlnc
1 da~ at RT 1.58 1.04
.42
3 days at RT 1.5~ 0.63
Table III p.uVIl~8~ stubi~ity results on the col..po~i~;on outllned in TAhh r c~f
Ex~mple 1 ~wlth and witho~Jt fluorlde~. From the resul~ It c~n be seen th~t ~Incc~ate h~ a st~lizin~ effoct upon the ~el co,.l~,o~;l;on In the pre~ence of
10 ffuoride ion. ~ca"enl % reco~,ery ot hydro~en pOf~: 'd~ 18 ~ d ~e~plte
stors~o ot tho formuls tT~ble I1 a~ 105~F for oi.len~sd poriods of tlnle.
The ~or~oln~ des~.lptlGn and Examples illustrate ~tle~ed embodln)en~s of the
pr~sent in~r~nllon. In ll~ht Il,ereof, varlous modlfl~l6n~ wlll be su~e~t~ to
15 one skllled In tl~ ~rt. ell of which are withln the splrl~ ~nd purvlew of thls
lu-.,nt-Q.~
